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[肉碱及肉碱转运体在中枢神经系统中的生理功能]

[Physiological functions of carnitine and carnitine transporters in the central nervous system].

作者信息

Inazu Masato, Matsumiya Teruhiko

机构信息

Department of Pharmacology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.

出版信息

Nihon Shinkei Seishin Yakurigaku Zasshi. 2008 Jun;28(3):113-20.

Abstract

L-Carnitine is an essential co-factor in the metabolism of lipids and consequently in the production of cellular energy. This molecule has important physiological roles, including its involvement in the beta-oxidation of fatty acids by facilitating the transport of long-chain fatty acids across the mitochondrial inner membrane as acylcarnitine esters. In the brain, L-carnitine and acetyl-L-carnitine have important roles in cerebral bioenergetics and in neuroprotection through a variety of mechanisms including their antioxidant properties and in the modulation and promotion of synaptic neurotransmission, most notably cholinergic neurotransmission. Acetyl-L-carnitine was successfully applied as pharmacological agents for treatment of chronic degenerative diseases of the senile brain and for slowing down the progression of mental deterioration in Alzheimer's disease, and they may involve both the cholinergic neuronal transmission activity of acetyl-L-carnitine and its ability to enhance neuronal metabolism in mitochondria. Astrocytes are able to produce large amounts of ketone bodies, which are thought to supply adjacent neurons with easily transferable substrates for generation of energy. Thus, the L-carnitine uptake mechanism becomes the rate-limiting step for astrocyte ketogenesis. Several carnitine transporters have been known to be present in peripheral tissues. In this review, the functional expression and physiological role of carnitine transporters in central nervous system is further discussed.

摘要

左旋肉碱是脂质代谢以及细胞能量产生过程中必不可少的辅助因子。该分子具有重要的生理作用,包括通过促进长链脂肪酸以酰基肉碱酯的形式穿过线粒体内膜参与脂肪酸的β氧化。在大脑中,左旋肉碱和乙酰左旋肉碱在脑生物能量学以及神经保护方面发挥着重要作用,其作用机制多种多样,包括抗氧化特性以及对突触神经传递(尤其是胆碱能神经传递)的调节和促进作用。乙酰左旋肉碱已成功用作治疗老年脑慢性退行性疾病以及减缓阿尔茨海默病精神衰退进程的药物,这可能涉及乙酰左旋肉碱的胆碱能神经元传递活性及其增强线粒体中神经元代谢的能力。星形胶质细胞能够产生大量酮体,这些酮体被认为可为相邻神经元提供易于转移的能量生成底物。因此,左旋肉碱摄取机制成为星形胶质细胞生酮作用的限速步骤。已知外周组织中存在几种肉碱转运体。在本综述中,将进一步讨论肉碱转运体在中枢神经系统中的功能表达和生理作用。

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